Fundamentals of Enzyme Kinetics: Michaelis-Menten and Non-Michaelis-Type (Atypical) Enzyme Kinetics

Abstract

This chapter will provide a general introduction to the kinetics of enzyme-catalyzed reactions, including a general discussion of catalysts, reaction rates, and binding constants. This section will be followed by a discussion of various types of enzyme kinetics observed in drug metabolism reactions. A large number of enzymatic reactions can be adequately described by Michaelis-Menten kinetics. The Michaelis-Menten equation represents a rectangular hyperbola, with a y-asymptote at the V_max value. However, in other cases, more complex kinetic models are required to explain the observed data. Atypical kinetic profiles are believed to arise from the simultaneous binding of multiple molecules within the active site of the enzyme (Tracy and Hummel, Drug Metab Rev 36:231-242, 2004). Several cytochromes P450 (CYPs) have large active sites that enable binding of multiple molecules (Yano et al., J Biol Chem 279:38091-38094, 2004; Wester et al., J Biol Chem 279:35630-35637, 2004). Thus, atypical kinetics are not uncommon in in vitro drug metabolism studies.

Keywords: Autoactivation; Binding constant; Biphasic kinetics; Catalysis; Eadie-Hofstee plot; Effector; Enzyme; Half-life; Heterotropic cooperativity; Homotropic cooperativity; Inhibitor; Lineweaver-Burk plot; Michaelis-Menten equation; Multienzyme kinetics; Nonlinear regression; Rate constant; Reaction rate; Substrate; Substrate inhibition.